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Glucose Turnover and Recycling in Diabetes Secondary to Total Pancreatectomy: Effect of Glucagon Infusion^*

Cattedra di Malattie del Ricambio, University of Padoua Padova, Italy

Address all correspondence and requests for reprints to: Stefano Del Prato, Cattedra di Malattie del Ricambio, Via Giustiniani, 2-35128 Padova, Italy

This study was designed to evaluate whether chronic deficiency of pancreatic glucagon in patients with diabetes secondary to total pancreatectomy (PX) is responsible for the commonly observed increase in blood concentrations of gluconeogenic precursors (alanine, lactate, and pyruvate). Seven PX patients were studied on two different occasions: 1) after an overnight insulin infusion (0.15 mU/kg·min) and 2) after an overnight insulin/glucagon infusion (2 ng/kg·min). Five type 1 diabetic individuals were also studied after a similar overnight insulin infusion. In the morning of each study day, [6-³H]glucose and [1-¹⁴C]glucose were rapidly injected for determination of total glucose turnover rate ([6-³H]glucose) and glucose recycling (difference between [6-³H]glucose and [1-¹⁴C]glucose turnover rate). Basal concentrations of hormones, glucose, and intermediary metabolites were measured. After overnight insulin infusion, plasma glucose concentration (3.8 ± 0.4 vs. 6.8 ± 1.4 mmol/L), turnover rate (8.4 ± 1.0 vs. 13.7 ± 1.9 µmol/kg·min), and percent glucose recycling (5.6 ± 3.9% vs. 19.0 ± 3.8%) were significantly lower in PX patients than in type 1 diabetic individuals (P < 0.05–0.01). On the contrary, blood alanine (459 ± 93 vs. 263 ± 28 µmol/L), lactate (1157 ± 109 vs. 818 ± 116 µmol/L), and pyruvate (71 ± 8 vs. 42 ± 3 µmol/L) were significantly higher than those values in type 1 diabetic patients (P < 0.05–0.01). Insulin/glucagon infusion increased plasma glucose con centration (8.7 ± 1.5 mmol/L), total turnover (18.1 ± 1.7 µmol/ kg·min), and percent recycling (20.4 ± 6.6%) to values similar to those in type 1 diabetic subjects. The change in glucose metabolism was associated with a significant drop in blood concentrations of alanine (179 ± 24 µmol/L), lactate (611 ± µmol/L), and pyruvate (30 ± 3 µmol/L; all P < 0.05–0.01 vs. insulin infusion alone). In PX patients, the glucose turnover rate was inversely correlated with blood concentrations of both alanine (r = 0.67) and lactate (r = 0.71; P < 0.01). In conclusion, chronic deficiency of pancreatic glucagon in PX patients 1) associated with a decreased rate of glucose turnover, 2) causes marked impairment in glucose recycling (an index of the activity of hepatic gluconeogenesis), and 3) increases blood concentra tions of alanine, lactate, and pyruvate. All abnormalities reversed by glucagon.

^* This work was supported by the Consiglio Nazionale delle Ricerche (Grants CNR 83.0285756 and 84.0255156).

Received June 21, 1989.

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